Neuronal survival and neurite elongation, two key components of neural regeneration, are likely to depend on the availability to the neurons of appropriate tropic stimuli. Nerve Growth Factor (NGF) has served for 30 years as a model for such neuronotrophic factors. Neuronotrophic activities other than NGF have been observed in several tissue extracts and culture-conditioned media, which address neurons from several peripheral ganglia and--more rarely--from various CNS tissues. We have identified and purified a new ciliary neuronotrophic factor CNTF, directed to the cholinergic neurons of chick embryo ciliary ganglia, in the extract of intraocular tissues that are innervated by these neurons. CNTF activity has also been recognized in extracts of peripheral nerve and CNS tissues, and found to accumulate in the fluid surrounding damaged nerve or brain. We have purified, on a pilot scale, the CNTF from mammalian (rat) sciatic nerve with similar biological but distinct physicochemical properties as those of the chick eye CNTF. We plan to continue the investigation of these several factors, particularly with regard to i) scaled-up production of both avian and mammalian CNTFs for both in vivo and in vitro uses, ii) generation of anti-CNTF antibodies, iii) use of molecular biology techniques to sequence the factor proteins, clone their genes and messenger RNAs, and attempt bioengineering production of the factors, iv) screening of other CNTFs by a new blot-and-culture technique and v) exploration of structural and biological properties of the purified CNTF.
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